MAb PGT121 protects against mucosal SHIV challenge in macaques at concentrations corresponding to its highly potent in vitro neutralization capacity

Background We recently characterized several new broadly neutralizing monoclonal antibodies (bnMAbs) remarkable for their in vitro potency. A number of these bnMAbs are almost 10 fold more potent than previously isolated bnMAbs such as PG9 and VRC01 and hundred fold more potent than older prototype bnMAbs such as 2G12 and b12. Of the new antibodies, PGT121 is one of the most broad and potent, and recognizes a glycan-dependent epitope. Based on in vitro neutralization potency, we speculated that PGT121 may be protective in vivo at serum concentrations below those previously determined for other broadly neutralizing anti-HIV antibodies. Methods The neutralization potency of PGT121 against SHIV SF162P3 was evaluated using a TZMbl-based neutralization assay. To evaluate the protective potency of PGT121 in vivo, we then designed a protection study in rhesus macaques. Animals were administered intravenously with 3 different doses of antibody (5 mg/kg, 1 mg/kg or 0.2 mg/kg) 24 hours before being vaginally challenged with a single high dose of SHIV SF162P3 (300 TCID50). Serum levels of antibody and viral loads were determined throughout the study.